TIGAR Ameliorates Pulmonary Ischemia-Reperfusion Injury by Activating PI3K/Akt Signaling Pathway

Aiping Xu, Xiuli Xia, Ting Xu, Ruxia Liu

Article ID: 7255
Vol 37, Issue 4, 2023
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20233704.201
Received: 9 May 2023; Accepted: 9 May 2023; Available online: 9 May 2023; Issue release: 9 May 2023

Abstract

Background and Purpose: Lung ischemia/reperfusion injury (LIRI) is common during early postoperative periods. However, the effects of TP53-induced glycolysis and apoptosis regulator (TIGAR) on LIRI in vivo and its associated mechanism of action are still undefined. We focus on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB, also known as Akt) pathway to elucidate the underlying mechanism of TIGAR in LIRI in this study. Methods: We constructed a LIRI rat model through blockade of the left pulmonary artery for 1 h, followed by 5 h of reperfusion. Lentiviral vectors encoding TIGAR (LV-TIGAR) or PI3K/Akt pathway inhibitor (LY294002) was injected into LIRI rats to examine the protective effects of TIGAR on LIRI and the related mechanism. TIGAR expression, pathological changes of lung tissue, PI3K/Akt activation, reactive oxygen species (ROS) production and inflammation were assessed in both lung tissue and in bronchoalveolar lavage fluid. Results: We found that TIGAR is down-regulated in LIRI rats, and restoration of its expression can improve the pathological changes of lung tissue in rats, the oxygen partial pressure (PO2) and carbon dioxide partial pressure (PCO2) to normal levels. Exogenous TIGAR overexpression also reduced the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), total leukocyte counts, the content of malondialdehyde (MDA) and ROS, but increased the activity of catalase (CAT) in peri-operative myocardial injury (PIMI) rats. Furthermore, LV-TIGAR increased the levels of PI3K and p-Akt/Akt in LIRI rats, and the protective effects of TIGAR in response to PIMI were alleviated by LY294002 in vivo. Conclusions: These findings demonstrate that overexpression of TIGAR exerts protective roles in the lungs of rats with PIMI through the activation of the PI3K/Akt signaling pathway.


Keywords

TIGAR;pulmonary ischemia-reperfusion injury;phosphatidylinositol 3-kinase;oxidative stress;inflammation


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